Promoter nucleosome dynamics regulated by signaling through the CTD code

  1. Philippe Materne
  2. Jayamani Anandhakumar
  3. Valerie Migeot
  4. Ignacio Soriano
  5. Carlo Yague-Sanz
  6. Elena Hidalgo
  7. Carole Mignion
  8. Luis Quintales
  9. Francisco Antequera
  10. Damien Hermand  Is a corresponding author
  1. University of Namur, Belgium
  2. LSU Health Sciences Center, United States
  3. Universidad de Salamanca, Spain
  4. Universitat Pompeu Fabra, Spain

Abstract

The phosphorylation of the RNA polymerase II CTD plays a key role in delineating transcribed regions within chromatin by recruiting histone methylases and deacetylases. Using genome-wide nucleosome mapping, we show that CTD S2 phosphorylation controls nucleosome dynamics in the promoter of a subset of 324 genes, including the regulators of cell differentiation ste11 and metabolic adaptation inv1. Mechanistic studies on these genes indicate that during gene activation a local increase of phosphoS2 CTD nearby the promoter impairs the phosphoS5 CTD dependent recruitment of Set1 and the subsequent recruitment of specific HDACs, which leads to nucleosome depletion and efficient transcription. The early increase of phosphoS2 results from the phosphorylation of the CTD S2 kinase Lsk1 by MAP kinase in response to cellular signaling. The artificial tethering of the Lsk1 kinase at the ste11 promoter is sufficient to activate transcription. Therefore, signaling through the CTD code regulates promoter nucleosomes dynamics.

Article and author information

Author details

  1. Philippe Materne

    Namur Research College, University of Namur, Namur, Belgium
    Competing interests
    The authors declare that no competing interests exist.
  2. Jayamani Anandhakumar

    Department of Biochemistry and Molecular Biology, LSU Health Sciences Center, Shreveport, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Valerie Migeot

    Namur Research College, University of Namur, Namur, Belgium
    Competing interests
    The authors declare that no competing interests exist.
  4. Ignacio Soriano

    Instituto de Biología Funcional y Genómica, Consejo Superior de Investigaciones Científicas, Universidad de Salamanca, Salamanca, Spain
    Competing interests
    The authors declare that no competing interests exist.
  5. Carlo Yague-Sanz

    Namur Research College, University of Namur, Namur, Belgium
    Competing interests
    The authors declare that no competing interests exist.
  6. Elena Hidalgo

    Departament de Ciencies Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain
    Competing interests
    The authors declare that no competing interests exist.
  7. Carole Mignion

    Namur Research College, University of Namur, Namur, Belgium
    Competing interests
    The authors declare that no competing interests exist.
  8. Luis Quintales

    Instituto de Biología Funcional y Genómica, Consejo Superior de Investigaciones Científicas, Universidad de Salamanca, Salamanca, Spain
    Competing interests
    The authors declare that no competing interests exist.
  9. Francisco Antequera

    Instituto de Biología Funcional y Genómica, Consejo Superior de Investigaciones Científicas, Universidad de Salamanca, Salamanca, Spain
    Competing interests
    The authors declare that no competing interests exist.
  10. Damien Hermand

    Namur Research College, University of Namur, Namur, Belgium
    For correspondence
    Damien.Hermand@unamur.be
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Danny Reinberg, Howard Hughes Medical Institute, New York University School of Medicine, United States

Publication history

  1. Received: May 26, 2015
  2. Accepted: June 19, 2015
  3. Accepted Manuscript published: June 22, 2015 (version 1)
  4. Version of Record published: July 15, 2015 (version 2)

Copyright

© 2015, Materne et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 2,598
    Page views
  • 633
    Downloads
  • 14
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Philippe Materne
  2. Jayamani Anandhakumar
  3. Valerie Migeot
  4. Ignacio Soriano
  5. Carlo Yague-Sanz
  6. Elena Hidalgo
  7. Carole Mignion
  8. Luis Quintales
  9. Francisco Antequera
  10. Damien Hermand
(2015)
Promoter nucleosome dynamics regulated by signaling through the CTD code
eLife 4:e09008.
https://doi.org/10.7554/eLife.09008

Further reading

    1. Chromosomes and Gene Expression
    2. Immunology and Inflammation
    Suhas Sureshchandra, Brianna M Doratt ... Ilhem Messaoudi
    Research Article Updated

    Maternal pre-pregnancy (pregravid) obesity is associated with adverse outcomes for both mother and offspring. Amongst the complications for the offspring is increased susceptibility and severity of neonatal infections necessitating admission to the intensive care unit, notably bacterial sepsis and enterocolitis. Previous studies have reported aberrant responses to LPS and polyclonal stimulation by umbilical cord blood monocytes that were mediated by alterations in the epigenome. In this study, we show that pregravid obesity dysregulates umbilical cord blood monocyte responses to bacterial and viral pathogens. Specifically, interferon-stimulated gene expression and inflammatory responses to respiratory syncytial virus (RSV) and E. coli were significantly dampened, respectively . Although upstream signaling events were comparable, translocation of the key transcription factor NF-κB and chromatin accessibility at pro-inflammatory gene promoters following TLR stimulation was significantly attenuated. Using a rhesus macaque model of western style diet-induced obesity, we further demonstrate that this defect is detected in fetal peripheral monocytes and tissue-resident macrophages during gestation. Collectively, these data indicate that maternal obesity alters metabolic, signaling, and epigenetic profiles of fetal monocytes leading to a state of immune paralysis during late gestation and at birth.

    1. Chromosomes and Gene Expression
    2. Plant Biology
    Myeongjune Jeon, Goowon Jeong ... Ilha Lee
    Research Article

    To synchronize flowering time with spring, many plants undergo vernalization, a floral-promotion process triggered by exposure to long-term winter cold. In Arabidopsis thaliana, this is achieved through cold-mediated epigenetic silencing of the floral repressor, FLOWERING LOCUS C (FLC). COOLAIR, a cold-induced antisense RNA transcribed from the FLC locus, has been proposed to facilitate FLC silencing. Here, we show that C-repeat (CRT)/dehydration-responsive elements (DREs) at the 3′-end of FLC and CRT/DRE-binding factors (CBFs) are required for cold-mediated expression of COOLAIR. CBFs bind to CRT/DREs at the 3′-end of FLC, both in vitro and in vivo, and CBF levels increase gradually during vernalization. Cold-induced COOLAIR expression is severely impaired in cbfs mutants in which all CBF genes are knocked-out. Conversely, CBF-overexpressing plants show increased COOLAIR levels even at warm temperatures. We show that COOLAIR is induced by CBFs during early stages of vernalization but COOLAIR levels decrease in later phases as FLC chromatin transitions to an inactive state to which CBFs can no longer bind. We also demonstrate that cbfs and FLCΔCOOLAIR mutants exhibit a normal vernalization response despite their inability to activate COOLAIR expression during cold, revealing that COOLAIR is not required for the vernalization process.